New strategy of platelet substitutes for enhancing platelet aggregation at high shear rates: Cooperative effects of a mixed system of fibrinogen γ-chain dodecapeptide- or glycoprotein Ibα-conjugated latex beads under flow conditions

Yosuke Okamura, Makoto Handa, Hidenori Suzuki, Yasuo Ikeda, Shinji Takeoka

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    To construct platelet substitutes that have hemostatic properties over a wide range of shear rates, we used fibrinogen γ-chain carboxy-terminal sequence HHLGGAKQAGDV (H12), which recognizes activated platelets at low shear rates, and a recombinant water-soluble moiety of the platelet glycoprotein (rGPIbα), which recognizes von Willebrand factor at high shear rates. Three kinds of samples were prepared for this purpose: H12-conjugated latex beads (H12-latex beads), rGPIbα-latex beads, and H12/rGPIbα-latex beads. These samples were evaluated in thrombocytopenia-imitation blood at various flow conditions. Based on ADP-induced platelet aggregation studies, the H12-latex beads significantly enhanced platelet aggregation via H12 binding with GPIIb/IIIa activated on the surface of activated platelets, whereas the rGPIbα-latex beads did not support platelet aggregation. In the case of the H12/rGPIbα-latex beads, the function of H12 was suppressed by steric hindrance from the larger rGPIbα bound to the latex bead. A mixture of the H12-latex beads and the rGPIbα-latex beads adhered to a collagen surface over a wide range of shear rates. In particular, at high shear rates, a cooperative effect was observed in the enhancement of platelet thrombus formation compared with H12-latex beads or rGPIbα-latex beads alone. We propose that a mixed system of H12- and rGPIbα-conjugated nanoparticles is a more effective platelet substitute than each of the beads used alone and has enhanced platelet aggregation properties.

    Original languageEnglish
    Pages (from-to)251-258
    Number of pages8
    JournalJournal of Artificial Organs
    Volume9
    Issue number4
    DOIs
    Publication statusPublished - 2006 Dec

    Fingerprint

    Platelet Glycoprotein GPIb-IX Complex
    Glycoproteins
    Latex
    Platelets
    Latexes
    Microspheres
    Platelet Aggregation
    Shear deformation
    Fibrinogen
    Blood Platelets
    Agglomeration
    Platelet Membrane Glycoproteins
    Administrative data processing
    von Willebrand Factor
    Hemostatics
    Collagen
    Thrombocytopenia
    Nanoparticles
    Adenosine Diphosphate
    Thrombosis

    Keywords

    • Fibrinogen γ-chain dodecapeptide
    • Platelet glycoprotein (GP) Ibα
    • Platelet substitute
    • Shear rate
    • Thrombocytopenia-imitation blood

    ASJC Scopus subject areas

    • Biophysics

    Cite this

    @article{13761fad5eab4cbdb0cf66ed71e62c36,
    title = "New strategy of platelet substitutes for enhancing platelet aggregation at high shear rates: Cooperative effects of a mixed system of fibrinogen γ-chain dodecapeptide- or glycoprotein Ibα-conjugated latex beads under flow conditions",
    abstract = "To construct platelet substitutes that have hemostatic properties over a wide range of shear rates, we used fibrinogen γ-chain carboxy-terminal sequence HHLGGAKQAGDV (H12), which recognizes activated platelets at low shear rates, and a recombinant water-soluble moiety of the platelet glycoprotein (rGPIbα), which recognizes von Willebrand factor at high shear rates. Three kinds of samples were prepared for this purpose: H12-conjugated latex beads (H12-latex beads), rGPIbα-latex beads, and H12/rGPIbα-latex beads. These samples were evaluated in thrombocytopenia-imitation blood at various flow conditions. Based on ADP-induced platelet aggregation studies, the H12-latex beads significantly enhanced platelet aggregation via H12 binding with GPIIb/IIIa activated on the surface of activated platelets, whereas the rGPIbα-latex beads did not support platelet aggregation. In the case of the H12/rGPIbα-latex beads, the function of H12 was suppressed by steric hindrance from the larger rGPIbα bound to the latex bead. A mixture of the H12-latex beads and the rGPIbα-latex beads adhered to a collagen surface over a wide range of shear rates. In particular, at high shear rates, a cooperative effect was observed in the enhancement of platelet thrombus formation compared with H12-latex beads or rGPIbα-latex beads alone. We propose that a mixed system of H12- and rGPIbα-conjugated nanoparticles is a more effective platelet substitute than each of the beads used alone and has enhanced platelet aggregation properties.",
    keywords = "Fibrinogen γ-chain dodecapeptide, Platelet glycoprotein (GP) Ibα, Platelet substitute, Shear rate, Thrombocytopenia-imitation blood",
    author = "Yosuke Okamura and Makoto Handa and Hidenori Suzuki and Yasuo Ikeda and Shinji Takeoka",
    year = "2006",
    month = "12",
    doi = "10.1007/s10047-006-0345-0",
    language = "English",
    volume = "9",
    pages = "251--258",
    journal = "Journal of Artificial Organs",
    issn = "1434-7229",
    publisher = "Springer Japan",
    number = "4",

    }

    TY - JOUR

    T1 - New strategy of platelet substitutes for enhancing platelet aggregation at high shear rates

    T2 - Cooperative effects of a mixed system of fibrinogen γ-chain dodecapeptide- or glycoprotein Ibα-conjugated latex beads under flow conditions

    AU - Okamura, Yosuke

    AU - Handa, Makoto

    AU - Suzuki, Hidenori

    AU - Ikeda, Yasuo

    AU - Takeoka, Shinji

    PY - 2006/12

    Y1 - 2006/12

    N2 - To construct platelet substitutes that have hemostatic properties over a wide range of shear rates, we used fibrinogen γ-chain carboxy-terminal sequence HHLGGAKQAGDV (H12), which recognizes activated platelets at low shear rates, and a recombinant water-soluble moiety of the platelet glycoprotein (rGPIbα), which recognizes von Willebrand factor at high shear rates. Three kinds of samples were prepared for this purpose: H12-conjugated latex beads (H12-latex beads), rGPIbα-latex beads, and H12/rGPIbα-latex beads. These samples were evaluated in thrombocytopenia-imitation blood at various flow conditions. Based on ADP-induced platelet aggregation studies, the H12-latex beads significantly enhanced platelet aggregation via H12 binding with GPIIb/IIIa activated on the surface of activated platelets, whereas the rGPIbα-latex beads did not support platelet aggregation. In the case of the H12/rGPIbα-latex beads, the function of H12 was suppressed by steric hindrance from the larger rGPIbα bound to the latex bead. A mixture of the H12-latex beads and the rGPIbα-latex beads adhered to a collagen surface over a wide range of shear rates. In particular, at high shear rates, a cooperative effect was observed in the enhancement of platelet thrombus formation compared with H12-latex beads or rGPIbα-latex beads alone. We propose that a mixed system of H12- and rGPIbα-conjugated nanoparticles is a more effective platelet substitute than each of the beads used alone and has enhanced platelet aggregation properties.

    AB - To construct platelet substitutes that have hemostatic properties over a wide range of shear rates, we used fibrinogen γ-chain carboxy-terminal sequence HHLGGAKQAGDV (H12), which recognizes activated platelets at low shear rates, and a recombinant water-soluble moiety of the platelet glycoprotein (rGPIbα), which recognizes von Willebrand factor at high shear rates. Three kinds of samples were prepared for this purpose: H12-conjugated latex beads (H12-latex beads), rGPIbα-latex beads, and H12/rGPIbα-latex beads. These samples were evaluated in thrombocytopenia-imitation blood at various flow conditions. Based on ADP-induced platelet aggregation studies, the H12-latex beads significantly enhanced platelet aggregation via H12 binding with GPIIb/IIIa activated on the surface of activated platelets, whereas the rGPIbα-latex beads did not support platelet aggregation. In the case of the H12/rGPIbα-latex beads, the function of H12 was suppressed by steric hindrance from the larger rGPIbα bound to the latex bead. A mixture of the H12-latex beads and the rGPIbα-latex beads adhered to a collagen surface over a wide range of shear rates. In particular, at high shear rates, a cooperative effect was observed in the enhancement of platelet thrombus formation compared with H12-latex beads or rGPIbα-latex beads alone. We propose that a mixed system of H12- and rGPIbα-conjugated nanoparticles is a more effective platelet substitute than each of the beads used alone and has enhanced platelet aggregation properties.

    KW - Fibrinogen γ-chain dodecapeptide

    KW - Platelet glycoprotein (GP) Ibα

    KW - Platelet substitute

    KW - Shear rate

    KW - Thrombocytopenia-imitation blood

    UR - http://www.scopus.com/inward/record.url?scp=33845681193&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=33845681193&partnerID=8YFLogxK

    U2 - 10.1007/s10047-006-0345-0

    DO - 10.1007/s10047-006-0345-0

    M3 - Article

    C2 - 17171404

    AN - SCOPUS:33845681193

    VL - 9

    SP - 251

    EP - 258

    JO - Journal of Artificial Organs

    JF - Journal of Artificial Organs

    SN - 1434-7229

    IS - 4

    ER -